gpc3/mesothelin/claudin18.2/gucy2c/b7-h3/psca/psma/muc1/tgfβ/her2/lewis-y/axl/egfr-car-t cells against cancers

Conditions: Lung Cancer; Cancer; Immunotherapy; CAR-T Cell

Summary: the third generation of car-t cells that target gpc3, mesothelin, claudin18.2, gucy2c, b7-h3, psca, psma, muc1, tgfβ, her2, lewis-y, axl, or egfr have been constructed respectively and their anti-cancer function has been verified by multiple in vitro and in vivo studies.clinical studies will be performed to test the anti-cancer function of the these individual or combination of the car-t cells for immunotherapy of human cancer patients with gpc3, mesothelin, claudin18.2, gucy2c, b7-h3, psca, psma, muc1, tgfβ, her2, lewis-y, axl, or egfr expressions. in this phase i study, the safety, tolerance, and preliminary efficacy of the gpc3/mesothelin/claudin18.2/gucy2c/b7-h3/psca/psma/muc1/tgfβ/her2/lewis-y/axl/egfr -car-t cell immunotherapy on human cancers will firstly be tested.

1. choose appropriate patients with advanced lung or other cancers,with written consent for this study; 2. perform biopsy to determine the expression of her2, mesothelin, lewis-y, psca, muc1, gpc3, axl, egfr, claudin18.2, or b7-h3 of the tumor by western blotting or ihc; 3. collect blood from the patients and isolate mononuclear cells, activate the t cells and transfect the t cells with gpc3, mesothelin, claudin18.2, gucy2c, b7-h3, psca, psma, muc1, tgfβ, her2, lewis-y, axl, or egfr targeting car, amplify the transfected t cells as needed, test the quality and killing activity of the car-t cells and then transfer them back the patients via systemic or local injections, and follow up closely to collect related results as needed; 4. to enhance the killing capability, cd4+ t cells are genetically engineered to express tgfβ-car and secret il7/ccl19 and/or scfvs against pd1/ctla4/tigit; cd8+t cells are constructed to express gpc3/mesothelin/claudin18.2/gucy2c/b7-h3/psca/psma/muc1/tgfβ/her2/lewis-y/axl/egfr -dap10-car with knockdown of pd1/hpk1; 5. other cancers with these cell surface antigen expressions are also recruited if needed; 6. evaluate the clinical results as needed.

Eligibility criteria:
inclusion criteria: 1. patients with advanced cancer that expresses gpc3/mesothelin/claudin18.2/gucy2c/b7-h3/psca/psma/muc1/tgfβ/her2/lewis-y/axl/egfr protein; 2. life expectancy \>12 weeks; 3. adequate heart,lung,liver,kidney function; 4. available autologous transduced t cells with greater than or equal to 20% expression ofgpc3, mesothelin, claudin18.2, gucy2c, b7-h3, psca, psma, muc1, tgfβ, her2, lewis-y, axl, or egfr-car determined by flow-cytometry and killing of gpc3, mesothelin, claudin18.2, gucy2c, b7-h3, psca, psma, muc1, tgfβ, her2, lewis-y, axl, or egfr-positive targets greater than or equal to 20% in cytotoxicity assay; 5. informed consent explained to, understood by and signed by patient/guardian. patient/guardian given copy of informed consent. - exclusion criteria: 1. had accepted gene therapy before; 2. severe virus infection such as hbv,hcv,hiv,et al; 3. known hiv positivity; 4. active infectious disease related to bacteria, virus,fungi,et al; 5. other severe diseases that the investigators consider not appropriate; 6. pregnant or lactating women; 7. systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day); 8. other conditions that the investigators consider not appropriate. -

Keywords: lung cancer car-t cell therapy psca muc1 her2 mesothelin lewis-y gpc3 axl egfr b7-h3 claudin18.2 tgfβ dap10 hpk1 pd1 ctla4 tigit knockdown scfv